A segmentation server configures and distributes rules for enforcing a segmentation policy that includes one or more virtual patches. The rules including the virtual patches are enforced by distributed enforcement modules that may execute on host devices or on network devices upstream from the host devices. An enforcement module enforces the rules using traffic filters that filter traffic based on network layer data. To implement a virtual patch, the traffic filters are configured to redirect traffic to or from an application being patched to a transparent application proxy. The transparent application proxy implements an application layer filter that filters traffic based on application layer data to block specific types of traffic associated with a vulnerability addressed by the virtual patch.